“Advocates on both sides have strong cases for their point of view that cannot simply be dismissed,” Mr. Schumer, Democrat of New York, said in a lengthy statement. “This has made evaluating the agreement a difficult and deliberate endeavor, and after deep study, careful thought and considerable soul-searching, I have decided I must oppose the agreement and will vote yes on a motion of disapproval.”

Mr. Schumer had spent the last several weeks carrying a dog-eared copy of the agreement in his briefcase and meeting with Mr. Obama and officials like Wendy R. Sherman, the deal’s chief negotiator. With his decision, he paves the way for other Democrats on the fence to join Republicans in showing their disapproval.

“There are some who believe that I can force my colleagues to vote my way,” Mr. Schumer said. “While I will certainly share my view and try to persuade them that the vote to disapprove is the right one, in my experience with matters of conscience and great consequence like this, each member ultimately comes to their own conclusion.”

As if on cue, Representative Eliot L. Engel of New York, the ranking Democrat on the House Foreign Affairs Committee, who was widely expected to oppose the deal, announced his opposition Thursday night.

Mr. Schumer said his chief concern was that Iran would still be free after a decade to build a nuclear bomb. His announcement comes as Representative Nancy Pelosi of California, the minority leader, labors to build a firewall in the House in support of the deal, which has been denounced by Prime Minister Benjamin Netanyahu of Israel. At six meetings in recent weeks, Ms. Pelosi has assembled an informal team of Democrats determined to win over the 146 House Democrats needed to uphold a veto.

But Ms. Pelosi’s team had had its eye on Mr. Schumer, conceded Representative Jan Schakowsky, Democrat of Illinois and one of Ms. Pelosi’s deputies on the Iran deal. Ms. Schakowsky said that Democratic leaders had never put Mr. Schumer “in the ‘yes’ column,” but that “the calculation still is we’ll have the votes” even without him.

So far, 12 Senate Democrats and one Democratic-leaning independent, Senator Angus King of Maine, have announced their support for the deal. Two others, Senator Bernie Sanders, a liberal independent from Vermont, and Senator Jack Reed of Rhode Island, the ranking Democrat on the Armed Services Committee, have all but announced their support.

Support from Mr. King, Senator Tim Kaine of Virginia and Senator Bill Nelson of Florida had given momentum to the accord. And an announcement Thursday by Senator Kirsten E. Gillibrand, Democrat of New York, that she would support the deal had also provided a boost.

But Mr. Obama needs 34 votes to sustain a promised veto of legislation disapproving the deal, which Republican leaders in the House and the Senate have promised to pass in September.

A veto override would be an enormous blow to the president’s prestige. It would torpedo an agreement between Iran and six powers — Britain, China, France, Germany, Russia and the United States — but it would not necessarily lead to the reimposition of crippling economic sanctions on Iran, supporters of the deal warn. With the other world powers supporting the agreement, the international sanctions regime would be likely to crumble, leaving the United States with far less effective tools to cripple Iran’s nuclear ambitions.

With so much on the line, Senate Democrats on the Foreign Relations Committee like Mr. Kaine had hoped to not only rally the 34 senators needed to sustain a presidential veto, but also to possibly keep enough Democrats behind the president to filibuster a resolution of disapproval next month. To do that, they most likely could lose only five Democrats. Mr. Schumer’s break with Mr. Obama will make that far more difficult.

Like many Jewish Democrats, Mr. Schumer approached the agreement under pressure from his constituents, the administration, and his own personal history and faith.

Besides individual meetings with Mr. Obama, Ms. Sherman and Secretary of State John Kerry, Mr. Schumer had three hourlong meetings with members of the negotiating team during which he received answers to 14 pages’ worth of questions on the agreement.

Ultimately, Mr. Schumer wrote his statement on his decision alone in his Senate office with a pen and yellow legal pad.

“I examined this deal in three parts: nuclear restrictions on Iran in the first 10 years, nuclear restrictions on Iran after 10 years, and nonnuclear components and consequences of a deal,” he wrote. “In each case I have asked: Are we better off with the agreement or without it?”

Mr. Schumer said that the inspection regime in the first 10 years of the agreement would be too weak, and that provisions to reimpose sanctions if Iran cheated were too onerous. He said his most serious concerns were with the freedom that Iran would have after 10 years to quickly build a nuclear weapon.

“To me, after 10 years, if Iran is the same nation as it is today, we will be worse off with this agreement than without it,” he said.

A version of this article appears in print on , Section A, Page 1 of the New York edition with the headline: Schumer Opposes Iran Deal, Shaking Democratic Firewall . Order Reprints | Today’s Paper | Subscribe